Rat brain contains insulin-like peptide and binding sites recognized by insulin. Using olfactory bulb slices we have found that cAMP content can be increased by either insulin or dopamine (DA). The insulin-dependent accumulation of cAMP was facilitated by sulpiride but was unaffected by haloperidol. Simultaneous addition of insulin and DA failed to increase cAMP when GppNHp was present, indicating that insulin interacts with DA and that insulin may be a neuromodulator for DA. We are now studying the synaptic location and transcriptional regulation of mRNA's for insulin-like peptide using a cDNA probe prepared from a bacterial clone synthesizing rat proinsulin. Since internalization of insulin may be a mechanism that explain interactions between DA and insulin in rat brain, we have also studied insulin internalization using frog erythrocytes as a model system. Using erythrocytes incubated with 125I-insulin, we have found a temperature dependent and energy required accumulation of radioactivity in the intracellular fraction. Morphologically we were also able to visualize insulin internalization using cells incubated with rhodamine-labeled with insulin. Studies are in progress to clarify the molecular mechanisms and functional significant of this insulin internalization.